This chapter focuses on structural MS and how the application of novel fragmentation methods, namely Electron-driven Dissociation (ExD) and UV Photo-Dissociation (UVPD) approaches, have transformed our capabilities to analyse biomolecular structure. A particularly active field in this respect is hydrogen/deuterium exchange (HDX), where electron-mediated fragmentation can enable deuterium labelling readouts with high spatial resolution. Top-down approaches take obvious benefit from a panoply of alternative, orthogonal dissociation techniques, bringing us closer to the goal of routinely achieving full sequence coverage of diverse proteoforms. In addition, native top-down approaches can link details of protein sequence with aspects of higher-order structure, particularly the extent of the solvent-accessible surface area. Lastly, MS/MS-cleavable crosslinkers are briefly discussed with the example of an Electron Transfer Dissociation (ETD-cleavable) linker applied to the GroEL-GroES chaperonin complex.